Synthesis of certain pyrazolol [3,4-d] pyrimidine derivatives of potential anti-inflammatory activity

The synthesis of twenty nine novel derivatives of pyrazolol [3,4-d] pyrimidines as non acidic nonsteroidal anti-inflammatory drugs has been achieved via reaction of 4-chloro-l-phenylpyrazolo [3,4-d] pyrimidine with different substituents including 4-amino-3-methylphenol, 4-phenylene diamine and 4-acetamidophenol. The anti-inflammatory activity of thirteen representative compounds have been screened compared to indomethacin as a reference drug. The results revealed that all the tested compounds showed anti-inflammatory activity with the exception of 10a.

Synthesis and pharmacological screening of certain imidazoquinazolone derivatives

Certain imidazoquinazolin-5[4H]-one derivatives have been synthesized by replacement of the 4-amino group compound I with different moieties of expected biological activity. Representative example of the synthesized compounds were tested for their anti-inflammatory, analgesic, antipyretic and anticonvulsant activities. Certain derivatives showed activities higher than that of the reference drugs

Synthesis and antineoplastic activity of certain triazene and triazeno-acridine combilexin derivatives

Four series of bifunctional ligands have been synthesized as DNA-binding combilexins. These novel agents contain a triazeno-benzene sulfonamide linker moiety that is attached to an intercalating acridine or acridone chromophore by a functionalized amide or ester residue. In order to obtain these combilexins three series of the anticipated antitumor triazeno-benzene sulfonamide were synthesized. The synthesis and bioscreening of the new antineoplastic compounds are depending on the structural correlation with several reported antineoplastic acridines. 2-Chlorobenzoic acid was reacted with anthranilic acid to give N-[2-carboxyphenyl] anthranilic acid which upon cyclodehydration with sulfuric acid afforded 9-oxo-9, 10-dihydroacridine-4-carboxylic acid, [acridone-4-carboxylic acid] 8. This latter intermediate has been converted to 9-chloroacridine carbonyl chloride 9 using thionyl chloride. Selective substitution of 9 with derivatives of 4-[piperazine-l-yldiazenyl] benzenesulfonamides 4a-e or derivatives of 4-[2-hydroxyethyl] piperazine-l-yl]diazenyi] benzenesulfonamides 5a-e to yield their 9-chloroacridine-4-carboxamides 10a-e and 9-chloroacridine-4-carboxylic acid esters 13a-e respectively. Those intermediates have been reacted either with different sulfonamides to give derivatives of 4-[4-[4-[4 sulfamoylphenyldiazenyl] piperazine-l-carbonyl]-9-ylamino] benz-enesulfonamides 11a-h and derivatives of 2-[[4-[4-sulfamoyl-phenyl]diazenyl]piperazine-l-yl]ethyl 9-[4-sulfamoylphenyl-amino]-9,10-dihydroacridine-4-carboxylates 14a-i respectively or subjected to mild acid hydrolysis to yield derivatives of 4-[4-[[9-oxo-9,1 Q-dihydroacridine-4-carbonyl]piperazine-l-yl]diazenyl]-benzenesulfonamide 12a-e and derivatives of 2-[4-[[4-sulfamoyl-phenyl]diazenyl]piperazine-l-yl]ethyl-9-oxo-9,10-dihydroacridine-4-carboxylate 15a-e respectively. Besides, the synthesis of derivatives of 4-[piperazine-l-yldiazenyl] benzenesulfonamides 4a-e and derivatives of 4-[2-hydroxyethyl]piperazine-1-yl] diazenyl] benzenesulfonamides 5a-e has been achieved via diazotization of various substituted benzene sulfonamides with sodium nitrite and hydrochloric acid followed by various amines coupling to yield the target triazeno-benzene sulfonamides. Fourteen new compounds were selected for screening their antitumor activity against breast cell line in National Cancer Institute. Six of them were found to be active as antitumor agents, while two were found to be mild active

Design and synthesis of certain imidazo[1,5-a] quinazolin-5 [4H]-ones of anticipated anticonvulsant activity

1 -[alkyl/aryl] - 3 - [1 - [4' -chlorophenyl] - 5 [4H] - oxo - imidazo [l,5-a]quinazolin-4-yl] thiourea 5 derivatives were synthesized from 4-amino-1-[4'-chlorophenyl] imidazo [1,5-a] quinazolin-5[4H]-one 4 which were cyclized into the corresponding thioxoimidazolidindiones 6, thiazolidinones 7 and 8, or 2,3-dihydrothiazol-4-ol 9. Also, some derivatives 10 were synthesized through the reaction of 4 with 5[4H]-oxazolone derivatives. Furthermore, 2-chloro-N-[l -[4'-chlorophenyl]-5[4H]-oxoimidazo[1,5-a] quinazolin-4-yl]acetamide 11 was reacted with sodium valproate or potassium 2-or 4-[3-substituted phenyl or cyclohexyl ureido]benzoate derivatives to give 12 or 13, respectively. Molecular modeling study was achieved to reveal the anticonvulsant activity of the newly synthesized derivatives postulating a hypothesis based on the specific binding with benzodiazepine receptor. Representative examples were chosen and screened for their anticonvulsant activity